The application of radiolabelled bioactive peptides for diagnostic imaging is gaining importance in nuclear medicine. Biologically active molecules which selectively interact with specific cell types are useful for the delivery of radioactivity to target tissues. For example, radiolabelled peptides have significant potential for the delivery of radionuclides to tumours, infarcts, and infected tissues for diagnostic imaging and radiotherapy. 18F, with its half-life of 110 minutes, is the positron-emitting nuclide of choice for many receptor imaging studies. Therefore, 18F-labelled bioactive peptides have great clinical potential because of their utility in PET to quantitatively detect and characterise a wide variety of diseases.
WO 99/11590 describes methods for [18F]fluorination of thiol containing peptides and proteins.
One difficulty with 18F-labelled peptides is that the existing 18F-labelling agents are time-consuming to prepare. Efficient labelling of peptides and proteins with 18F is only achieved by using suitable prosthetic groups. Several such prosthetic groups have been proposed in the literature, including N-succinimidyl-4-[18F]fluorobenzoate, m-maleimido-N-(p-[18F]fluorobenzyl)-benzamide, N-(p-[18F]fluorophenyl) maleimide, and 4-[18F]fluorophenacylbromide. Almost all of the methodologies currently used today for the labelling of peptides and proteins with 18F utilise active esters of the fluorine labelled synthon. As peptides and proteins may contain a multitude of functional groups capable of reaction with active esters these current methods are not site-specific. For example a peptide containing 3 lysine residues has three amine functions all equally reactive towards the labelled synthon. Therefore, there still exists a need for 18F-labelled prosthetic groups and methodologies which allow rapid, chemoselective introduction of 18F, particularly into peptides, under mild conditions to give 18F-labelled products in high radiochemical yield and purity. Additionally, there is a need for such methodologies which are amenable to automation to facilitate preparation of radiopharmaceuticals in the clinical setting.